Naslov
Analysis of conserved residues of the human dipeptidyl peptidase III

Autori
Špoljarić, Jasminka ; Salopek-Sondi, Branka ; Vukelić, Bojana ; Jajčanin Jozić, Nina ; Makarević, Janja ; Agić, Dejan ; Šimaga, Šumski ; Vujaklija, Dušica ; Abramić, Marija

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
VIII European Symposium of The Protein Society / Pluckthun, A ; Aebersold, R ; Engel, A ; Helenius, A ; Hilvert, D ; Richmond, T ; Schuler, B - Zürich : The Protein Society ; University of Zurich, 2009, 172-172

Skup
VIII European Symposium of The Protein Society

Mjesto i datum
Zürich, Švicarska, 14.06.2009. - 18.06.2009

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
peptidase family M49; dipeptidyl peptidase III; hydroxamate inhibitor; protein structure-function; site-directed mutagenesis

Sažetak
The dipeptidyl peptidase III (DPP III) is a zinc-exopeptidase and a member of the metallopeptidase family M49 with an implied role in the pain-modulating system and endogenous defense against oxidative stress. The role of the unique fully conserved tyrosine (Tyr318) and tryptophan (Trp300) was investigated in human enzyme by site-directed mutagenesis. The substitution of Tyr318 for Phe decreased kcat by two orders of magnitude without altering the binding affinity of substrate or of a competitive inhibitor. However, replacement of the Trp300 reduced enzyme activity and had a negative effect on the binding of two competitive hydroxamate inhibitors designed to interact with S1 and S2 subsites. The results indicate that the conserved tyrosine could be involved in transition state stabilization during the catalytic action of M49 peptidases, and that conserved tryptophan contributes in maintaining the functional integrity of the enzyme's S2 subsite.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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